{"id":"https://openalex.org/W7223559092","doi":"https://doi.org/10.64898/2026.10.21.760783","title":"Targeting cyclic-AMP/phosphodiesterase signaling to quiet nasal tuft cell calcium responses","display_name":"Targeting cyclic-AMP/phosphodiesterase signaling to quiet nasal tuft cell calcium responses","publication_year":2026,"publication_date":"2026-10-25","ids":{"openalex":"https://openalex.org/W7223559092","doi":"https://doi.org/10.64898/2026.10.21.760783"},"language":"en","primary_location":{"id":"doi:10.64898/2026.10.21.760783","doi":"https://doi.org/10.64898/2026.10.21.760783","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.21.760783","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/25/2026.10.21.760783.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/25/2026.10.21.760783.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5093637342","display_name":"Kyle Polen","orcid":"https://orcid.org/0009-0003-7775-111X","observed_orcids":["https://orcid.org/0009-0003-7775-111X"]},"institutions":[{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kyle Polen","raw_affiliation_strings":["Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA"],"raw_orcid":"https://orcid.org/0009-0003-7775-111X","affiliations":[{"raw_affiliation_string":"Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA","institution_ids":["https://openalex.org/I79576946"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5052173242","display_name":"Li Eon Kuek","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Li Eon Kuek","raw_affiliation_strings":["Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA","institution_ids":["https://openalex.org/I79576946"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5025469656","display_name":"Zhongming Ma","orcid":"https://orcid.org/0000-0002-6404-6214","observed_orcids":["https://orcid.org/0000-0002-6404-6214"]},"institutions":[{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Zhongming Ma","raw_affiliation_strings":["Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA","institution_ids":["https://openalex.org/I79576946"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110477224","display_name":"Nithin D. Adappa","orcid":"https://orcid.org/0000-0002-0339-8769","observed_orcids":["https://orcid.org/0000-0002-0339-8769"]},"institutions":[{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Nithin D. Adappa","raw_affiliation_strings":["Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA","institution_ids":["https://openalex.org/I79576946"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5027109682","display_name":"James N. Palmer","orcid":"https://orcid.org/0000-0002-7535-9339","observed_orcids":["https://orcid.org/0000-0002-7535-9339"]},"institutions":[{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"James N. Palmer","raw_affiliation_strings":["Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA","institution_ids":["https://openalex.org/I79576946"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5061187034","display_name":"Ryan M. Carey","orcid":"https://orcid.org/0000-0002-0186-2265","observed_orcids":["https://orcid.org/0000-0002-0186-2265"]},"institutions":[{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ryan M. Carey","raw_affiliation_strings":["Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA"],"raw_orcid":"https://orcid.org/0000-0002-0186-2265","affiliations":[{"raw_affiliation_string":"Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA","institution_ids":["https://openalex.org/I79576946"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5040022220","display_name":"Robert J. Lee","orcid":"https://orcid.org/0000-0001-5826-6686","observed_orcids":["https://orcid.org/0000-0001-5826-6686"]},"institutions":[{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Robert J. Lee","raw_affiliation_strings":["Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA","Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA"],"raw_orcid":"https://orcid.org/0000-0001-5826-6686","affiliations":[{"raw_affiliation_string":"Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA","institution_ids":["https://openalex.org/I79576946"]},{"raw_affiliation_string":"Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA","institution_ids":["https://openalex.org/I79576946"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5040022220"],"corresponding_institution_ids":["https://openalex.org/I79576946"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10984","display_name":"Sinusitis and nasal conditions","score":0.6557999849319458,"subfield":{"id":"https://openalex.org/subfields/2733","display_name":"Otorhinolaryngology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10984","display_name":"Sinusitis and nasal conditions","score":0.6557999849319458,"subfield":{"id":"https://openalex.org/subfields/2733","display_name":"Otorhinolaryngology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T12434","display_name":"Phosphodiesterase function and regulation","score":0.15230000019073486,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10971","display_name":"Olfactory and Sensory Function Studies","score":0.0471000000834465,"subfield":{"id":"https://openalex.org/subfields/2809","display_name":"Sensory Systems"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/camp-signaling","display_name":"cAMP signaling","score":0.8560000061988831},{"id":"https://openalex.org/keywords/pde2a","display_name":"PDE2A","score":0.9430000185966492},{"id":"https://openalex.org/keywords/calcium-signaling","display_name":"calcium signaling","score":0.8939999938011169},{"id":"https://openalex.org/keywords/g-protein-coupled-receptors","display_name":"G protein-coupled receptors","score":0.875},{"id":"https://openalex.org/keywords/bitter-taste-receptors","display_name":"bitter taste receptors","score":0.8619999885559082},{"id":"https://openalex.org/keywords/adenosine-a1-receptor","display_name":"adenosine A1 receptor","score":0.8240000009536743},{"id":"https://openalex.org/keywords/sucnr1","display_name":"SUCNR1","score":0.8740000128746033},{"id":"https://openalex.org/keywords/il-25","display_name":"IL-25","score":0.8939999938011169},{"id":"https://openalex.org/keywords/chronic-rhinosinusitis-with-nasal-polyps","display_name":"chronic rhinosinusitis with nasal polyps","score":0.9269999861717224},{"id":"https://openalex.org/keywords/ciliary-beat-frequency","display_name":"ciliary beat frequency","score":0.7710000276565552},{"id":"https://openalex.org/keywords/trpm5","display_name":"TRPM5","score":0.7120000123977661},{"id":"https://openalex.org/keywords/pertussis-toxin","display_name":"pertussis toxin","score":0.7300000190734863}],"concepts":[{"id":"https://openalex.org/C2777128398","wikidata":"https://www.wikidata.org/wiki/Q7851514","display_name":"Tuft","level":2,"score":0.8435999751091003},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.6504999995231628},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.5504000186920166},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4462999999523163},{"id":"https://openalex.org/C24998067","wikidata":"https://www.wikidata.org/wiki/Q4114622","display_name":"Stimulation","level":2,"score":0.41280001401901245},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.4025999903678894},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.4002000093460083},{"id":"https://openalex.org/C2909851952","wikidata":"https://www.wikidata.org/wiki/Q2673594","display_name":"Nasal passages","level":3,"score":0.38760000467300415},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.3783999979496002},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.3626999855041504},{"id":"https://openalex.org/C2781390199","wikidata":"https://www.wikidata.org/wiki/Q8055111","display_name":"Nasal polyps","level":2,"score":0.3334999978542328},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.3138999938964844},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.3082999885082245},{"id":"https://openalex.org/C135285700","wikidata":"https://www.wikidata.org/wiki/Q38173","display_name":"G protein-coupled receptor","level":3,"score":0.29490000009536743},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.2793000042438507},{"id":"https://openalex.org/C105702510","wikidata":"https://www.wikidata.org/wiki/Q514","display_name":"Anatomy","level":1,"score":0.27709999680519104}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.10.21.760783","doi":"https://doi.org/10.64898/2026.10.21.760783","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.21.760783","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/25/2026.10.21.760783.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.10.21.760783","doi":"https://doi.org/10.64898/2026.10.21.760783","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.21.760783","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/25/2026.10.21.760783.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"score":0.8999999761581421,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320309370","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10"},{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320337365","display_name":"National Institute of Dental and Craniofacial Research","ror":"https://ror.org/004a2wv92"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7223559092.pdf","grobid_xml":"https://content.openalex.org/works/W7223559092.grobid-xml"},"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W3097165642","https://openalex.org/W2804651205","https://openalex.org/W7222983854","https://openalex.org/W2800773914","https://openalex.org/W3211740017","https://openalex.org/W1597455958","https://openalex.org/W2095016073","https://openalex.org/W2605251370","https://openalex.org/W2110763080","https://openalex.org/W2786746578"],"abstract_inverted_index":{"Abstract":[0],"Background":[1],"Airway":[2],"tuft":[3,65,86,159,209,235,247],"cells,":[4,9,87],"also":[5,50,166,237],"called":[6],"solitary":[7],"chemosensory":[8],"are":[10,16,34],"enriched":[11,189],"in":[12,25,81,94,155,207,257],"nasal":[13,29,85,97,158,213,234],"polyps":[14,30],"and":[15,73,88,108,115,147,162,169,196,201,224,240,252],"likely":[17],"the":[18,57,143,148],"main":[19],"epithelial":[20,98],"source":[21],"of":[22,138],"interleukin-25":[23],"(IL-25)":[24],"chronic":[26],"rhinosinusitis":[27],"with":[28,105],"(CRSwNP).":[31],"Tuft":[32,186],"cells":[33,187,236],"activated":[35],"through":[36,43,244],"G":[37],"protein-coupled":[38],"receptors":[39,48,141],"(GPCRs)":[40],"that":[41,232],"signal":[42],"Ca":[44,71,89,153,204,219,249],"2+":[45,72,90,154,205,220,250],".":[46,192],"These":[47],"may":[49],"lower":[51,238],"cyclic":[52],"AMP":[53],"(cAMP),":[54],"but":[55],"whether":[56],"cAMP":[58,74,200,243],"pathway":[59],"can":[60],"be":[61],"used":[62],"to":[63],"suppress":[64],"cell":[66,79,132,248],"responses":[67,91,206],"is":[68],"unknown.":[69],"Methods":[70],"were":[75,92,111,172,188,255],"measured":[76,93,112],"by":[77,113,120,174,241],"live":[78],"imaging":[80],"isolated":[82],"Trpm5-GFP":[83],"mouse":[84,157,208],"primary":[95],"human":[96,212],"air-liquid":[99],"interface":[100],"(ALI)":[101],"cultures":[102],"from":[103],"patients":[104],"CRSwNP.":[106],"Defensin":[107],"IL-25":[109,225,253],"release":[110,226,254],"ELISA":[114],"ciliary":[116],"beat":[117],"frequency":[118],"(CBF)":[119],"high-speed":[121],"imaging.":[122],"Phosphodiesterase":[123],"(PDE)":[124],"expression":[125],"was":[126],"assessed":[127],"using":[128],"publicly":[129],"available":[130],"single":[131],"RNA":[133],"sequencing":[134],"datasets.":[135],"Results":[136],"Agonists":[137],"bitter":[139],"taste":[140,180],"(T2Rs),":[142],"succinate":[144],"receptor":[145,151,164],"SUCNR1,":[146],"A1":[149,163],"adenosine":[150],"increased":[152,184,199],"GFP-positive":[156],"cells.":[160,210],"T2R":[161],"stimulation":[165],"lowered":[167],"cAMP,":[168,239],"these":[170],"decreases":[171],"blocked":[173],"pertussis":[175],"toxin.":[176],"Glucose,":[177],"which":[178],"activates":[179],"family":[181],"1":[182],"receptors,":[183],"cAMP.":[185],"for":[190],"Pde2a":[191],"PDE2A-selective":[193],"inhibitors":[194],"(PF-05180999":[195],"BAY":[197],"60-7550)":[198],"reduced":[202,217,256],"agonist-evoked":[203],"In":[211],"ALIs,":[214],"both":[215],"compounds":[216],"denatonium-evoked":[218],"responses,":[221],"defensin":[222],"release,":[223],"without":[227],"increasing":[228],"CBF.":[229],"Conclusions":[230],"GPCRs":[231],"activate":[233],"raising":[242],"PDE2A":[245],"inhibition,":[246],"signaling":[251],"vitro.":[258]},"counts_by_year":[],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2026-10-26T00:00:00"}